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| 1 | Evaluation of acoustic radiation force impulse imaging for determination of liver stiffness using transient elastography as a reference显示文摘AIM: To evaluate cut-off values and performance of acoustic radiation force impulse imaging (ARFI) using transient elastography [FibroScan■ (FS)] as a reference. METHODS: Six hundred and six patients were enrolled in this study.All patients underwent liver stiffness measurement with FS (FS-LS) and ARFI (with shear wave velocity quantification; ARFI-SWV) and the performance of ARFI in comparison to FS was determined. Sixtyeight patients underwent liver biopsy. RESULTS: Significantly higher success rates for the determination of liver stiffness were found using ARFI as compared to FS [604/606 (99.7%) vs 482/606 (79.5%); P < 0.001]. ARFI-SWV correlated significantly with FS-LS (r = 0.920, P < 0.001). ARFI-SWV increased significantly with the stage of fibrosis (1.09 ± 0.13 m/s for patients with no significant fibrosis (FS-LS < 7.6 kPa); 1.46 ± 0.27 m/s for patients with significant liver fibrosis (7.6 < FS-LS ≤ 13.0 kPa); and 2.55 ± 0.77 m/s for patients with liver cirrhosis (FS-LS > 13.0 kPa)). ARFI-SWV cut-off values were identified for no significant fibrosis (1.29 m/s; sensitivity 91.4% and specificity 92.6%) and for liver cirrhosis (1.60 m/s; sensitivity 92.3% and specificity 96.5%). The optimal cut-off value for predicting liver fibrosis (F ≥ 2) was 1.32 m/s (sensitivity 87.0% and specificity 80.0%) and for liver cirrhosis (F4) 1.62 m/s (sensitivity 100% and specificity 85.7%), for patients who underwent liver biopsy. An excellent inter-and intraobserver reproducibility was observed for ARFI-SWV determinations. CONCLUSION: An ARFI-SWV cut-off value of 1.29 m/s seems to be optimal for patients with no significant liver fibrosis and 1.60 m/s for patients with liver cirrhosis. | Gerald Kircheis Abdurrahman Sagir Christoph Vogt Stephan vom Dahl Ralf Kubitz Dieter Hussinger | 2012 | World Journal of Gastroenterology2012，18，10： | 30 |
| 2 | Endocrine and paracrine role of bile acids显示文摘Bile acids are not only important for the absorption of dietary lipids and fat soluble vitamins but are signalling molecules with diverse endocrine and paracrine functions. Bile acids regulate bile acid, lipid and glucose metabolism and modulate temperature and energy homeostasis. Furthermore, bile acids can not only promote cell proliferation and liver regeneration but can also induce programmed cell death. Bile acid functions are mediated through different pathways which comprise the activation of nuclear hormone receptors, of intracellular kinases and of the plasma membrane-bound, G-protein coupled bile acid receptor TGR5/Gp-bar-1. | Verena Keitel Ralf Kubitz Dieter Hussinger | 2008 | World Journal of Gastroenterology2008，14，37： | 7 |
| 3 | Hepatitis B and D Viruses Exploit Sodium Taurocholate Co-transporting Polypeptide for Species-specific Entry into Hepatocytes显示文摘 | Yi Ni Florian A. Lempp Stefan Mehrle Shirin Nkongolo Christina Kaufman Maria F?lth Jan Stindt Christian K?niger Michael Nassal Ralf Kubitz Holger Sültmann Stephan Urban | 2013 | Gastroenterology2013，，： | 5 |
| 4 | Partial external biliary diversion in bile salt export pump deficiency: Association between outcome and mutation显示文摘AIM To investigate the relation of two different mutations to the outcome of partial external biliary diversion(PEBD)in severe bile salt export pump(BSEP) deficiency.METHODS Mutations in the gene encoding BSEP leading to severe BSEP deficiency in two unrelated patients were identified by genomic sequencing. Native liver biopsies and transiently transfected human embryonic kidney(HEK) 293 cells expressing either wild-type or mutated BSEP were subjected to immunofluorescence analysis to assess BSEP transporter localization. Bile acid profiles of patient and control bile samples were generated by ultra-performance liquid chromatographytandem mass spectrometry. Wild-type and mutant BSEP transport of [~3H]-labeled taurocholate(TC) and taurochenodeoxycholate(TCDC) was assessed by vesicular transport assays.RESULTS A girl(at 2 mo) presented with pruritus, jaundice and elevated serum bile salts(BS). PEBD stabilized liver function and prevented liver transplantation. She was heterozygous for the BSEP deletion p.T919 del and the nonsense mutation p.R1235 X. At the age of 17 years relative amounts of conjugated BS in her bile were normal, while total BS were less than 3% as compared to controls. An unrelated boy(age 1.5 years) presenting with severe pruritus and elevated serum BS was heterozygous for the same nonsense and another missense mutation, p.G1032 R. PEBD failed to alleviate pruritus, eventually necessitating liver transplantation. BS concentration in bile was about 5% of controls. BS were mainly unconjugated with an unusual low amount of chenodeoxycholate derivatives(< 5%). The patients' native liver biopsies showed canalicular BSEP expression. Both BSEP p.T919 del and p.G1032 R were localized in the plasma membrane in HEK293 cells. In vitro transport assays showed drastic reduction of transport by both mutations. Using purified recombinant BSEP as quantifiable reference, per-molecule transport rates for TC and TCDC were determined to be 3 and 2 BS molecules per wild-type BSEP transporter per minute, respectively.CONCLUSION In summary, our findings suggest that residual function of BSEP as well as substrate specificity influence the therapeutic effectiveness of PEBD in progressive familial intrahepatic cholestasis type 2(PFIC-2). | Philipp Ellinger Jan Stindt Carola Droge Katharina Sattler Claudia Stross Stefanie Kluge Diran Herebian Sander HJ Smits Martin Burdelski Sebastian Schulz-Jürgensen Antje Ballauff Jan Schulte am Esch Ertan Mayatepek Dieter Haussinger Ralf Kubitz Lutz Schmitt | 2017 | World Journal of Gastroenterology2017，23，29： | 4 |
| 5 | Strategies to Inhibit Entry of HBV and HDV Into Hepatocytes显示文摘 | Stephan Urban Ralf Bartenschlager Ralf Kubitz Fabien Zoulim | 2014 | Gastroenterology2014，，： | 3 |
| 6 | Influences on copper bioaccumulation,growth,and survival of the midge,Chironomus tentans,in metal-contaminated sediments显示文摘 | BESSER J M KUBITZ J A INGERSOLL C G | 1995 | J Aquatic Ecosystem Health1995，4，3： | 1 |
| 7 | The bile salt export pump (BSEP) in health and disease 显示文摘 | Kubitz R Droge C Stindt L | 2012 | Clin Res Hepatol Gastroenterol2012，36，6： | 1 |
| 8 | Activation of rat hepatic stellate cells in culture is associated with increased sensitivity to endothelin 1 显示文摘 | Reinehr RM Kubitz R Peters-Regehr T | 1998 | Hepatology1998，28，6： | 1 |
| 9 | Osmoregulation of Bile Formation显示文摘 | Ralf Kubitz Dieter H?ussinger | 2007 | Methods in Enzymology2007，，： | 1 |
| 10 | Validation of pulse contour derived stroke volume variation during modifications of cardiac afterload显示文摘 | Kubitz JC Annecke T Forkl S | 2007 | Br J Anaesth2007，98，5： | 1 |
| 11 | Functional hemodynamicparameters do not reflect volume responsiveness in the immediatephase after acute myocardial ischemia and reperfusion 显示文摘 | Kronas N Kubitz JC Forkl S | 2011 | JCardiothorac Vase Anesth2011，25，： | 1 |
| 12 | Strategies to inhibit entry of HBV and HDV into hepatocytes 显示文摘 | Urban S Bartenschlager R Kubitz R | 2014 | Gastroenterology2014，147，1： | 1 |
| 13 | The influence of positive end-expiratory pressure on stroke volume variation and central blood volume during open and closed chest conditions 显示文摘 | Kubitz JC Thorsten A Kemming GI | 2006 | Eur J Cardiothoracic Surg2006，30，1： | 1 |
| 14 | Symptomatic separation of pubic symphysis显示文摘 | Kubitz RL Goodlin RC | 1986 | South Med J1986，79，5： | 1 |
| 15 | Poor outcome in primary non-small cell lung cancers is predicted by transketolase TKTL1 expression显示文摘 | Kayser G Sienel W Kubitz B | 2011 | Pathology2011，43，7： | 1 |
| 16 | Client-server-based mobile robot control显示文摘 | O Kubitz M O Berger R Stenzel | 1998 | IEEE/ASME Transactions on Mechatronics1998，3，2： | 1 |
| 17 | The bile salt export pump (BSEP) in health and disease显示文摘 | Kubitz R Drge C Stindt J | 2012 | Clin Res Hepatol Gastroenterol2012，36，6： | 1 |
| 18 | Protein kinase C–dependent distribution of the multidrug resistance protein 2 from the canalicular to the basolateral membrane in human HepG2 cells显示文摘 | Ralf Kubitz Clemens Huth Marcus Schmitt Axel Horbach Gerd Kullak-Ublick Dieter H?ussinger | 2001 | Hepatology2001，，2： | 1 |
| 19 | Stable expression and functional characterization of a Na+-taurocholate cotransporting green fluorescent protein in human hepatoblastoma HepG2 cells显示文摘 | Gerd A. Kullak-Ublick Manfred G. Ismair Ralf Kubitz Marcus Schmitt Dieter H?ussinger Bruno Stieger Bruno Hagenbuch Peter J. Meier Ulrich Beuers Gustav Paumgartner | 2000 | Cytotechnology (-)2000，，1： | 1 |
| 20 | Psychomotor recovery in very old patients after total intravenous or balanced anaesthesia for eatarat surgery显示文摘 | Kubitz J Epple J Bach A | 2001 | Br J Anaesth2001，86，2： | 1 |
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